This proposal is an attempt to discover the mechanism by which melanocytes die prematurely in two genetic mutants as compared to the life span of these cells in wild type chickens. It is a study of developmental gene expression and we are trying to uncover the exact mechanism by which these genes carry out their function and to ascertain if these two mutants could be fowl models for vitiligo. The specific aim of this grant proposal is to test the hypothesis that genetic hypomelanosis occurs in the Barred Plymouth Rock (BPR) chicken and the White Leghorn (WL) chicken due to the influence of the barring gene and the dominant white gene, respectively. It is proposed that these genes cause the melanocytes of these breeds to be more sensitive (die easier) than melanocytes of the wild type breed. It is also proposed that a toxic substance is produced in these mutants which they are sensitive to and that WL melanocytes are less viable than BPR melanocytes due to a difference of these conditions. To test this hypothesis, the experimental design consists of four subdivisions. One, experiments are planned to prove that there is a sensitivity difference between the three genotypes (two mutants and wild type) and the mutant alleles (B/B, B/b+, B/- and I/I/,I/i+). Second, experiments will be performed to gather evidence that the toxic substance may be related to melanin precursor compounds. Third, experiments are planned to test the involvement of oxygen radicals (O2) in the viability of these genotypes. Fourth, experiments will be performed to see the effect of the two mutant genes, barring and dominant white and their alleles, on eye pigmentation, tyrosinase activity and a newly discovered enzyme (factor?) in the melanin synthesis pathway, dopachrome conversion factor (DCF); also termed dopachrome oxidoreductose (DCOR). MBRS students will be taught the techniques necessary to perform these experiments and data collection and analysis. The students will present their findings at national meetings and co-author any publication arising from their work. Hopefully this experience will influence a significant number of the students to enter graduate school and to pursue a research and/or teaching career.